Transcription of the gene for phosphoenolpyruvate carboxykinase is regulated by several hormones which control the level of glucose synthesis in vertebrate animals. A 490 bp segment located at the 5' end of the structural gene contains the necessary regulatory elements to account for the pattern of transcriptional regulation characteristic of the phosphoenolpyruvate carboxykinase gene. Multiple cis binding sites within the promoter and nuclear binding proteins have been identified and shown to play a role in the regulation of gene transcription. The interaction of these transcription factors with each other and with the phosphoenolpyruvate carboxykinase promoter is central to the regulated expression of this gene. The key role of cAMP and insulin in controlling the level of gene transcription will be discussed and related to the function of transcription factors currently known to regulate the tissue specific expression of the phosphoenolpyruvate carboxykinase gene.